JP2024510111A - 腫瘍の予防、軽減、又は治療方法 - Google Patents
腫瘍の予防、軽減、又は治療方法 Download PDFInfo
- Publication number
- JP2024510111A JP2024510111A JP2023550186A JP2023550186A JP2024510111A JP 2024510111 A JP2024510111 A JP 2024510111A JP 2023550186 A JP2023550186 A JP 2023550186A JP 2023550186 A JP2023550186 A JP 2023550186A JP 2024510111 A JP2024510111 A JP 2024510111A
- Authority
- JP
- Japan
- Prior art keywords
- amino acid
- seq
- heavy chain
- acid sequence
- her2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 208
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 157
- 230000000116 mitigating effect Effects 0.000 title claims description 5
- 229940125497 HER2 kinase inhibitor Drugs 0.000 claims abstract description 218
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 198
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 172
- 101000884345 Homo sapiens Cyclin-dependent kinase 12 Proteins 0.000 claims abstract description 109
- 102100038111 Cyclin-dependent kinase 12 Human genes 0.000 claims abstract description 106
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims abstract description 80
- 230000004075 alteration Effects 0.000 claims abstract description 49
- 239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 20
- 229940127557 pharmaceutical product Drugs 0.000 claims abstract description 20
- 230000005764 inhibitory process Effects 0.000 claims abstract description 16
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 310
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 260
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 224
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 213
- 230000027455 binding Effects 0.000 claims description 189
- 108090000623 proteins and genes Proteins 0.000 claims description 147
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 112
- 239000000427 antigen Substances 0.000 claims description 99
- 108091007433 antigens Proteins 0.000 claims description 99
- 102000036639 antigens Human genes 0.000 claims description 99
- 229920001184 polypeptide Polymers 0.000 claims description 99
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 99
- 102000004169 proteins and genes Human genes 0.000 claims description 98
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 93
- 239000000539 dimer Substances 0.000 claims description 84
- 238000012163 sequencing technique Methods 0.000 claims description 77
- 230000003321 amplification Effects 0.000 claims description 76
- 229940126601 medicinal product Drugs 0.000 claims description 74
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 claims description 72
- 102000048776 human CD274 Human genes 0.000 claims description 71
- 230000035772 mutation Effects 0.000 claims description 69
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 67
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 67
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 67
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 67
- 229960000575 trastuzumab Drugs 0.000 claims description 66
- 229960002087 pertuzumab Drugs 0.000 claims description 53
- 238000011282 treatment Methods 0.000 claims description 50
- PIMQWRZWLQKKBJ-SFHVURJKSA-N 2-[(2S)-1-[3-ethyl-7-[(1-oxido-3-pyridin-1-iumyl)methylamino]-5-pyrazolo[1,5-a]pyrimidinyl]-2-piperidinyl]ethanol Chemical compound C=1C(N2[C@@H](CCCC2)CCO)=NC2=C(CC)C=NN2C=1NCC1=CC=C[N+]([O-])=C1 PIMQWRZWLQKKBJ-SFHVURJKSA-N 0.000 claims description 47
- 101150059217 CDK12 gene Proteins 0.000 claims description 46
- 229950009859 dinaciclib Drugs 0.000 claims description 46
- 206010006187 Breast cancer Diseases 0.000 claims description 40
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 claims description 39
- 230000014509 gene expression Effects 0.000 claims description 39
- 230000008859 change Effects 0.000 claims description 38
- 208000026310 Breast neoplasm Diseases 0.000 claims description 37
- 108700020302 erbB-2 Genes Proteins 0.000 claims description 37
- 239000012634 fragment Substances 0.000 claims description 35
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 claims description 34
- 230000002401 inhibitory effect Effects 0.000 claims description 31
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 30
- 101150054472 HER2 gene Proteins 0.000 claims description 29
- 108020004999 messenger RNA Proteins 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 102000051957 human ERBB2 Human genes 0.000 claims description 26
- 108020004414 DNA Proteins 0.000 claims description 24
- 238000001514 detection method Methods 0.000 claims description 24
- 230000000903 blocking effect Effects 0.000 claims description 22
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 claims description 16
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 claims description 16
- 229960001612 trastuzumab emtansine Drugs 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 206010055113 Breast cancer metastatic Diseases 0.000 claims description 14
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 claims description 14
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 14
- 230000004614 tumor growth Effects 0.000 claims description 14
- 108060003951 Immunoglobulin Proteins 0.000 claims description 13
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 13
- 230000004927 fusion Effects 0.000 claims description 13
- 206010017758 gastric cancer Diseases 0.000 claims description 13
- 102000018358 immunoglobulin Human genes 0.000 claims description 13
- 201000011549 stomach cancer Diseases 0.000 claims description 13
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 12
- 229950003135 margetuximab Drugs 0.000 claims description 12
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 12
- 102000043321 human CTLA4 Human genes 0.000 claims description 11
- CEBMEQPREMCWOL-UHFFFAOYSA-N n-[(4,5-difluoro-1h-benzimidazol-2-yl)methyl]-9-(3-fluorophenyl)-2-morpholin-4-ylpurin-6-amine Chemical compound FC1=CC=CC(N2C3=NC(=NC(NCC=4NC5=CC=C(F)C(F)=C5N=4)=C3N=C2)N2CCOCC2)=C1 CEBMEQPREMCWOL-UHFFFAOYSA-N 0.000 claims description 11
- 210000005259 peripheral blood Anatomy 0.000 claims description 11
- 239000011886 peripheral blood Substances 0.000 claims description 11
- 230000008707 rearrangement Effects 0.000 claims description 11
- RUBYHLPRZRMTJO-MOVYNIQHSA-N THZ531 Chemical compound c1cc(NC(=O)/C=C/CN(C)C)ccc1C(=O)N1CCC[C@@H](Nc2ncc(Cl)c(n2)-c2c[nH]c3ccccc32)C1 RUBYHLPRZRMTJO-MOVYNIQHSA-N 0.000 claims description 10
- 238000000338 in vitro Methods 0.000 claims description 10
- 239000000178 monomer Substances 0.000 claims description 10
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 9
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 230000004962 physiological condition Effects 0.000 claims description 9
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 claims description 8
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 claims description 8
- 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 claims description 8
- 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 claims description 8
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 claims description 8
- 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 claims description 8
- 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 claims description 8
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 8
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 8
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 8
- 239000000710 homodimer Substances 0.000 claims description 8
- 229960004891 lapatinib Drugs 0.000 claims description 8
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 8
- SADXACCFNXBCFY-IYNHSRRRSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-ethoxyquinolin-6-yl]-3-[(2r)-1-methylpyrrolidin-2-yl]prop-2-enamide Chemical compound C=12C=C(NC(=O)\C=C\[C@@H]3N(CCC3)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 SADXACCFNXBCFY-IYNHSRRRSA-N 0.000 claims description 7
- SDEAXTCZPQIFQM-UHFFFAOYSA-N 6-n-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-4-n-[3-methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]quinazoline-4,6-diamine Chemical compound C=1C=C(OC2=CC3=NC=NN3C=C2)C(C)=CC=1NC(C1=C2)=NC=NC1=CC=C2NC1=NC(C)(C)CO1 SDEAXTCZPQIFQM-UHFFFAOYSA-N 0.000 claims description 7
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 229950008835 neratinib Drugs 0.000 claims description 7
- ZNHPZUKZSNBOSQ-BQYQJAHWSA-N neratinib Chemical compound C=12C=C(NC\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZNHPZUKZSNBOSQ-BQYQJAHWSA-N 0.000 claims description 7
- 229950003463 tucatinib Drugs 0.000 claims description 7
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 6
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 229940075576 pyrotinib Drugs 0.000 claims description 6
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 5
- 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 claims description 5
- 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 claims description 5
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 claims description 5
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 claims description 5
- 229960004117 capecitabine Drugs 0.000 claims description 5
- 229960003668 docetaxel Drugs 0.000 claims description 5
- 102000051255 human CDK12 Human genes 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 206010063916 Metastatic gastric cancer Diseases 0.000 claims description 3
- 102000008096 B7-H1 Antigen Human genes 0.000 claims 65
- 210000004881 tumor cell Anatomy 0.000 abstract description 25
- 230000004663 cell proliferation Effects 0.000 abstract 1
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 198
- 210000004027 cell Anatomy 0.000 description 49
- 150000001413 amino acids Chemical class 0.000 description 39
- 239000000523 sample Substances 0.000 description 23
- 238000006467 substitution reaction Methods 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 20
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 19
- 238000012217 deletion Methods 0.000 description 17
- 230000037430 deletion Effects 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 238000003780 insertion Methods 0.000 description 16
- 230000037431 insertion Effects 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 229940022353 herceptin Drugs 0.000 description 14
- 238000007481 next generation sequencing Methods 0.000 description 14
- 201000011510 cancer Diseases 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 102000001708 Protein Isoforms Human genes 0.000 description 11
- 108010029485 Protein Isoforms Proteins 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 10
- 238000003364 immunohistochemistry Methods 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 108091007914 CDKs Proteins 0.000 description 8
- 238000003734 CellTiter-Glo Luminescent Cell Viability Assay Methods 0.000 description 8
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 8
- 230000009422 growth inhibiting effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 241000283690 Bos taurus Species 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 230000000890 antigenic effect Effects 0.000 description 7
- 230000003993 interaction Effects 0.000 description 7
- 230000001394 metastastic effect Effects 0.000 description 7
- 150000007523 nucleic acids Chemical group 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- 241000282887 Suidae Species 0.000 description 6
- 239000000562 conjugate Substances 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- 101000946850 Homo sapiens T-lymphocyte activation antigen CD86 Proteins 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 238000012054 celltiter-glo Methods 0.000 description 5
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 5
- 102000054189 human CD80 Human genes 0.000 description 5
- 102000049849 human CD86 Human genes 0.000 description 5
- 102000048362 human PDCD1 Human genes 0.000 description 5
- 238000004020 luminiscence type Methods 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 5
- 108010058546 Cyclin D1 Proteins 0.000 description 4
- 206010059866 Drug resistance Diseases 0.000 description 4
- 238000012286 ELISA Assay Methods 0.000 description 4
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 4
- 206010061968 Gastric neoplasm Diseases 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- 239000000611 antibody drug conjugate Substances 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 238000009650 gentamicin protection assay Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- 238000011460 HER2-targeted therapy Methods 0.000 description 3
- 101100327356 Homo sapiens CDK12 gene Proteins 0.000 description 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 3
- 239000012980 RPMI-1640 medium Substances 0.000 description 3
- 108010003723 Single-Domain Antibodies Proteins 0.000 description 3
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 3
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 3
- 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000000090 biomarker Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 3
- 230000005750 disease progression Effects 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940049679 trastuzumab deruxtecan Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- 108060000903 Beta-catenin Proteins 0.000 description 2
- 102000015735 Beta-catenin Human genes 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- 102000016736 Cyclin Human genes 0.000 description 2
- 108050006400 Cyclin Proteins 0.000 description 2
- 108010058545 Cyclin D3 Proteins 0.000 description 2
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 2
- 102100038114 Cyclin-dependent kinase 13 Human genes 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101150029707 ERBB2 gene Proteins 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000884348 Homo sapiens Cyclin-dependent kinase 13 Proteins 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 description 2
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 2
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 2
- 108010087230 Sincalide Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 102000025171 antigen binding proteins Human genes 0.000 description 2
- 108091000831 antigen binding proteins Proteins 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 238000003491 array Methods 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 238000010609 cell counting kit-8 assay Methods 0.000 description 2
- 230000022131 cell cycle Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000012165 high-throughput sequencing Methods 0.000 description 2
- 230000003259 immunoinhibitory effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- KJBZQIKLKWQVLL-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[(7-methyl-7-azaspiro[3.5]nonan-2-yl)methoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCC11CC(COC=2C(=CC3=C(NC=4C=C(Cl)C(F)=CC=4)N=CN=C3C=2)NC(=O)C=C)C1 KJBZQIKLKWQVLL-UHFFFAOYSA-N 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 238000004393 prognosis Methods 0.000 description 2
- 108020001580 protein domains Proteins 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229940063683 taxotere Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- GJLXVWOMRRWCIB-MERZOTPQSA-N (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanoyl]amino]-6-aminohexanamide Chemical compound C([C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=C(O)C=C1 GJLXVWOMRRWCIB-MERZOTPQSA-N 0.000 description 1
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
- 101000840545 Bacillus thuringiensis L-isoleucine-4-hydroxylase Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 101150091609 CD274 gene Proteins 0.000 description 1
- 102100038078 CD276 antigen Human genes 0.000 description 1
- 101710185679 CD276 antigen Proteins 0.000 description 1
- 101150047910 CSNK1D gene Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 208000016718 Chromosome Inversion Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 108010068237 Cyclin H Proteins 0.000 description 1
- 102100036883 Cyclin-H Human genes 0.000 description 1
- 102100036876 Cyclin-K Human genes 0.000 description 1
- 102100023263 Cyclin-dependent kinase 10 Human genes 0.000 description 1
- 101710179260 Cyclin-dependent kinase 12 Proteins 0.000 description 1
- 102100038113 Cyclin-dependent kinase 14 Human genes 0.000 description 1
- 102100033245 Cyclin-dependent kinase 16 Human genes 0.000 description 1
- 102100033144 Cyclin-dependent kinase 18 Human genes 0.000 description 1
- 102100033145 Cyclin-dependent kinase 19 Human genes 0.000 description 1
- 102100034741 Cyclin-dependent kinase 20 Human genes 0.000 description 1
- 102100026810 Cyclin-dependent kinase 7 Human genes 0.000 description 1
- 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 230000033616 DNA repair Effects 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010066896 HER-2 positive gastric cancer Diseases 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
- 101100407305 Homo sapiens CD274 gene Proteins 0.000 description 1
- 101000713127 Homo sapiens Cyclin-K Proteins 0.000 description 1
- 101000908138 Homo sapiens Cyclin-dependent kinase 10 Proteins 0.000 description 1
- 101000884374 Homo sapiens Cyclin-dependent kinase 14 Proteins 0.000 description 1
- 101000944357 Homo sapiens Cyclin-dependent kinase 16 Proteins 0.000 description 1
- 101000944345 Homo sapiens Cyclin-dependent kinase 19 Proteins 0.000 description 1
- 101000945708 Homo sapiens Cyclin-dependent kinase 20 Proteins 0.000 description 1
- 101000911952 Homo sapiens Cyclin-dependent kinase 7 Proteins 0.000 description 1
- 101000980937 Homo sapiens Cyclin-dependent kinase 8 Proteins 0.000 description 1
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
- 101001037256 Homo sapiens Indoleamine 2,3-dioxygenase 1 Proteins 0.000 description 1
- 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
- 101001030211 Homo sapiens Myc proto-oncogene protein Proteins 0.000 description 1
- 102100026120 IgG receptor FcRn large subunit p51 Human genes 0.000 description 1
- 101710177940 IgG receptor FcRn large subunit p51 Proteins 0.000 description 1
- 102100040061 Indoleamine 2,3-dioxygenase 1 Human genes 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 102000002698 KIR Receptors Human genes 0.000 description 1
- 108010043610 KIR Receptors Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 101150018665 MAPK3 gene Proteins 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- 206010059282 Metastases to central nervous system Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 108010082739 NADPH Oxidase 2 Proteins 0.000 description 1
- 108010039798 PCTAIRE-3 protein kinase Proteins 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101001037255 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Indoleamine 2,3-dioxygenase Proteins 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
- 101100215487 Sus scrofa ADRA2A gene Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 108091005906 Type I transmembrane proteins Proteins 0.000 description 1
- 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 1
- 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000006037 cell lysis Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229940125808 covalent inhibitor Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000007847 digital PCR Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000011304 droplet digital PCR Methods 0.000 description 1
- 229960005501 duocarmycin Drugs 0.000 description 1
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 description 1
- 229930184221 duocarmycin Natural products 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000037828 epithelial carcinoma Diseases 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000007672 fourth generation sequencing Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 108091006104 gene-regulatory proteins Proteins 0.000 description 1
- 102000034356 gene-regulatory proteins Human genes 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 108091008039 hormone receptors Proteins 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 229940124644 immune regulator Drugs 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000030776 invasive breast carcinoma Diseases 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004777 loss-of-function mutation Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 238000007403 mPCR Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 201000011591 microinvasive gastric cancer Diseases 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000005375 negative regulation of lymphocyte activation Effects 0.000 description 1
- 208000029522 neoplastic syndrome Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 238000001558 permutation test Methods 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000092 prognostic biomarker Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000734 protein sequencing Methods 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000012070 whole genome sequencing analysis Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2827—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/91—Transferases (2.)
- G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNPCT/CN2021/077490 | 2021-02-23 | ||
CN2021077490 | 2021-02-23 | ||
PCT/CN2022/077313 WO2022179507A1 (en) | 2021-02-23 | 2022-02-22 | Methods of preventing, alleviating or treating tumors |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2024510111A true JP2024510111A (ja) | 2024-03-06 |
Family
ID=83047787
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023550186A Pending JP2024510111A (ja) | 2021-02-23 | 2022-02-22 | 腫瘍の予防、軽減、又は治療方法 |
Country Status (5)
Country | Link |
---|---|
US (1) | US20240101707A1 (zh) |
EP (1) | EP4298128A1 (zh) |
JP (1) | JP2024510111A (zh) |
CN (1) | CN116964096A (zh) |
WO (1) | WO2022179507A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023070160A1 (en) * | 2021-10-28 | 2023-05-04 | Monash University | Variant ctla4 proteins |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9345661B2 (en) * | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
CN110658340B (zh) * | 2015-01-08 | 2023-10-31 | 苏州康宁杰瑞生物科技有限公司 | 具有共同轻链的双特异性抗体或抗体混合物 |
CN110215516A (zh) * | 2018-03-02 | 2019-09-10 | 南京大学 | 一种抑制cdk5协同免疫治疗在抑制乳腺癌中的应用 |
TWI831789B (zh) * | 2018-06-05 | 2024-02-11 | 大陸商江蘇康寧杰瑞生物製藥有限公司 | 二聚體及其用途 |
-
2022
- 2022-02-22 EP EP22758871.2A patent/EP4298128A1/en active Pending
- 2022-02-22 WO PCT/CN2022/077313 patent/WO2022179507A1/en active Application Filing
- 2022-02-22 JP JP2023550186A patent/JP2024510111A/ja active Pending
- 2022-02-22 CN CN202280016300.1A patent/CN116964096A/zh active Pending
-
2023
- 2023-08-22 US US18/454,006 patent/US20240101707A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
CN116964096A (zh) | 2023-10-27 |
US20240101707A1 (en) | 2024-03-28 |
EP4298128A1 (en) | 2024-01-03 |
WO2022179507A1 (en) | 2022-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2020202712B2 (en) | Treatment of cancer with dual targeting of CD47 and EGFR | |
AU2018246873B2 (en) | ErbB-2 and ErbB3 binding bispecific antibodies for use in the treatment f cells that have an NRG1 fusion gene | |
JP6920989B2 (ja) | がんのための併用療法 | |
KR102418979B1 (ko) | Pd-1/pd-l1 신호전달을 방해하는 것에 의한 암 면역요법 | |
Nahta et al. | Herceptin: mechanisms of action and resistance | |
JP2021061838A (ja) | Ox40アゴニスト治療薬の有効性及び評価を予測するための方法及びバイオマーカー | |
JP2018518483A (ja) | 抗ox40抗体及びpd−1軸結合アンタゴニストを使用して癌を治療する方法 | |
JP2018521019A (ja) | 抗ox40抗体を使用して癌を治療する方法 | |
KR20180066236A (ko) | Icos 발현을 계측하기 위한 유전자 특질 | |
JP2018504610A (ja) | T細胞免疫サブセットを検出するためのアッセイ及びその使用の方法 | |
TW201731527A (zh) | 使用抗pd-1抗體與抗clta-4抗體之組合以治療肺癌 | |
US20240101707A1 (en) | A method of preventing, alleviating or treating a tumor | |
JP2023551602A (ja) | Tl1aを標的とする炎症性疾患の治療のための方法、システム、およびキット | |
CN113891748A (zh) | 治疗肿瘤的方法 | |
TW202130664A (zh) | 用於治療患有her2及her3陽性癌症之對象的手段及方法 | |
JP7494245B2 (ja) | Cd47及びegfrの二重標的化による癌治療 | |
US20240024320A1 (en) | Methods of treating cancer with a combination of tucatinib and an anti-pd-1/anti-pd-l1 antibody | |
US20240182587A1 (en) | Erbb-2 and erbb-3 binding bispecific antibodies for use in the treatment of cells that have an nrg1 fusion gene | |
TW202321309A (zh) | 使用至少結合egfr之抗體治療免疫檢查點抑制劑治療之具高egfr表現的癌症 | |
JP2024515879A (ja) | 抗siglec組成物及びその使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231023 |